Expression Of Homeobox B7Gene In Colon Carcinoma And Its Clinicopathological Significance

ObjectiveTo observer the expression of homeobox B7gene in colon cancer and explore its association with clinicopathological parameters and its prognostic significance for colon cancer patients after radical surgery.Methods(1) HOXB7mRNA level was detected in31cases of colon cancer mucosa and adjacent normal mucosa by real-time polymerase chain reaction (qRT-PCR).(2) HOXB7protein expression was detected by immunohistochemistry in73cases of colon cancer.(3) Chi-square (χ2) test or Fisher’s exract test were used to analyze the association between HOXB7protein expression and clinicopathological data. Survival curves were plotted by Kaplan-Meier curves with log-rank tests. In addition, univariate and multivariate Cox regression analyses was used to evaluated the effect of HOXB7upon prognosis in colon cancer.Results(1) In these31paired samples,21(67.74%) analyzed samples expressed a higher level of HOXB7mRNA in colon cancer tissue specimens than that in noncancerous tissue specimens, the difference is significant (P<0.01).(2) By immunohistochemistry, we observed that HOXB7protein was localized in the cytoplasm of colon cancer cells and HOXB7was up-regulated in colon cancer mucosa compared with paired nomal colon mucosa (64.4%(47/73)vs27.4%(20/73)), the difference is significant (P<0.01). (3) Association between HOXB7protein expression and clinicopathologic parameters in colon cancer:HOXB7protein expression is much higher in the group combining T3and T4than that in the group combining T1and T2(79.5%vs40.1%, P<0.01). HOXB7protein expression is also higher in patients with distant metastasis than that without distant metastasis (91.7%vs59.0%, P<0.05). The rate of HOXB7-positive staining in patients with AJCC Ⅲ and Ⅳ is significantly higher than that in patients with AJCC Ⅰ and Ⅱ (84.4%vs48.8%, P<0.01). Following the developing of AJCC stage, the expression of HOXB7protein was increasing subsequently. In addition, overexpression of HOXB7protein is significantly correlated with proliferating cell nuclear antigen (Ki-67) index (P<0.01), indicates that HOXB7might promote tumor cell proliferation.(4) Association of HOXB7protein expression with prognosis of patients with colon cancer after colectomy:Patients with HOXB7-negative patients had a better5-year diseasing-free survival (DFS) than that with HOXB7-positive patients [78.8%vs57.6%,P<0.05; hazard ratio (HR)3.517,95%confidence interval (CI):1.837-6.004, P<0.05];as well as the5-year overall survival (OS) of colon cancer patients [84.6%vs66.0%,P<0.05; HR,4.836;95%(CI):2.149-6.327, P<0.05]. In addition, based on the univariate analysis, AJCC stage, T stage, lymph node metastasis, distant metastasis, vascular invasion and poor differentiation were significantly associated with both OS and DFS (P<0.05). The follow up multivariate analysis also found AJCC stage, T stage, lymph node metastasis, distant metastasis and HOXB7expression were significantly corelated with both OS and DFS, suggesting HOXB7could serve as an independent prognostic marker.ConclusionOverexpression of HOXB7protein in colon cancer was significantly correlated with multiple clinicalpatholgoical factors and and survival in patients with colon cancer after colectomy, which suggest that HOXB7might be involved in colon cancer progression and could serve as a novel therapeutic biomarker, which migtht help to improve individual therapeutic decision-making.